Biogenetic mechanisms predisposing to complex phenotypes in parents may function differently in their children.
Ontology highlight
ABSTRACT:
SUBMITTER: Kulminski AM
PROVIDER: S-EPMC3674715 | biostudies-literature | 2013 Jul
REPOSITORIES: biostudies-literature
Publications
Biogenetic mechanisms predisposing to complex phenotypes in parents may function differently in their children.
Kulminski Alexander M AM Arbeev Konstantin G KG Christensen Kaare K Stallard Eric E Miljkovic Iva I Barmada Michael M Yashin Anatoliy I AI
The journals of gerontology. Series A, Biological sciences and medical sciences 20121204 7
This study focuses on the participants of the Long Life Family Study to elucidate whether biogenetic mechanisms underlying relationships among heritable complex phenotypes in parents function in the same way for the same phenotypes in their children. Our results reveal 3 characteristic groups of relationships among phenotypes in parents and children. One group composed of 3 pairs of phenotypes confirms that associations among some phenotypes can be explained by the same biogenetic mechanisms wor ...[more]
Similar Datasets
Project description:The genetic mechanisms of childhood development in its many facets remain largely undeciphered. In the population of healthy infants studied in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) program, we have identified a range of dependencies among the observed phenotypes of fetal and early childhood growth, neurological development, and a number of genetic variants. We have quantified these dependencies using our information theory-based methods. The genetic variants show dependencies with single phenotypes as well as pleiotropic effects on more than one phenotype and thereby point to a large number of brain-specific and brain-expressed gene candidates. These dependencies provide a basis for connecting a range of variants with a spectrum of phenotypes (pleiotropy) as well as with each other. A broad survey of known regulatory expression characteristics, and other function-related information from the literature for these sets of candidate genes allowed us to assemble an integrated body of evidence, including a partial regulatory network, that points towards the biological basis of these general dependencies. Notable among the implicated loci are RAB11FIP4 (next to NF1), MTMR7 and PLD5, all highly expressed in the brain; DNMT1 (DNA methyl transferase), highly expressed in the placenta; and PPP1R12B and DMD (dystrophin), known to be important growth and development genes. While we cannot specify and decipher the mechanisms responsible for the phenotypes in this study, a number of connections for further investigation of fetal and early childhood growth and neurological development are indicated. These results and this approach open the door to new explorations of early human development.
| S-EPMC7714163 | biostudies-literature
Project description:Purpose of reviewThe goal of the review is to provide a comprehensive overview of the current understanding of the mechanisms underlying variation in human stature.Recent findingsHuman height is an anthropometric trait that varies considerably within human populations as well as across the globe. Historically, much research focus was placed on understanding the biology of growth plate chondrocytes and how modifications to core chondrocyte proliferation and differentiation pathways potentially shaped height attainment in normal as well as pathological contexts. Recently, much progress has been made to improve our understanding regarding the mechanisms underlying the normal and pathological range of height variation within as well as between human populations, and today, it is understood to reflect complex interactions among a myriad of genetic, environmental, and evolutionary factors. Indeed, recent improvements in genetics (e.g., GWAS) and breakthroughs in functional genomics (e.g., whole exome sequencing, DNA methylation analysis, ATAC-sequencing, and CRISPR) have shed light on previously unknown pathways/mechanisms governing pathological and common height variation. Additionally, the use of an evolutionary perspective has also revealed important mechanisms that have shaped height variation across the planet. This review provides an overview of the current knowledge of the biological mechanisms underlying height variation by highlighting new research findings on skeletal growth control with an emphasis on previously unknown pathways/mechanisms influencing pathological and common height variation. In this context, this review also discusses how evolutionary forces likely shaped the genomic architecture of height across the globe.
| S-EPMC6819265 | biostudies-literature
Project description:BackgroundContinuity of care has been explored largely from academic and service provider perspectives, and in relation to adult patient/client groups. We interviewed parents of children with complex chronic health conditions to examine how their experiences and perceptions of continuity of care fit with these perspectives; and to identify the salient factors in the experience of, and factors contributing to, continuity in this population.MethodsParents of 47 elementary school-aged children with spina bifida, Down syndrome, attention-deficit/hyperactivity disorder, Duchenne muscular dystrophy or cystic fibrosis participated in semi-structured interviews. Parents described and mapped the pattern of their interactions with service providers over time in all domains relevant to their child's health, well-being, and development (medical, rehabilitational, educational, and social supportive services), with particular attention paid to their perceptions of connectedness or coherency in these interactions. Verbatim transcripts were analyzed thematically using a framework approach to impose structure regarding parents' perspectives on continuity of care.ResultsExisting academic concepts of relational, informational and management continuity were all discernable in parents' narratives. A thorough knowledge of the child on the part of service providers emerged as extremely important to parents; such knowledge was underpinned by continuity of personal relationships, principally, and also by written information. For this population, notions of continuity extend to the full range of service providers these children and families need to achieve optimal health status, and are not limited to physicians and nurses. Communication among providers was seen as integral to perceived continuity. Compartmentalization of services and information led to parents assuming a necessary, though at times, uncomfortable, coordinating role. Geographic factors, institutional structures and practices, provider attitudes, and, on occasion, parent preferences and judgments, were all found to create barriers to "seamless" management and provision of care continuity across providers, settings, and sectors.ConclusionsThese findings add new perspectives to the understanding of continuity within chronically ill children's health care. They are relevant to contemporary initiatives to improve continuity of services to children with special health care needs, demonstrate the need for parental support of their important role in maintaining continuity, and suggest avenues for further research.
| S-EPMC2805629 | biostudies-literature
Project description:Numerous molecular processes conduct epigenetic regulation of protein transcription to maintain cell specification. In this review, we discuss molecular mechanisms of the Polycomb group of proteins and its enzymatic role in epigenetics. More specifically, we focus on the Polycomb repressive complex 2 (PRC2) and the effects of its repressive marker. We have compiled information regarding the biological structure and how that impacts the stability of the complex. In addition, we examined functions of the individual core proteins of PRC2 in relation to the accessory proteins that interact with the complex. Lastly, we discuss the implications of unregulated and downregulated PRC2 activity in Alzheimer's disease and cancer and possible methods of treatment related to PRC2 regulation.
| S-EPMC6635771 | biostudies-literature
Project description:The study examined potential mediating effects of therapist behaviors in the per-protocol sample (n = 108) of a randomized controlled trial comparing a behavioral and a nondirective guided self-help intervention for parents of children with externalizing disorders (4-11 years). Additionally, from an exploratory perspective, we analyzed a sequential model with parental adherence as second mediator following therapist behavior. Outcomes were child symptom severity of attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder rated by blinded clinicians, and parent-rated child functional impairment. We found a significant indirect effect on the reduction of ADHD and functional impairment through emotion- and relationship-focused therapist behavior in the nondirective intervention. Additionally, we found limited support for an extended sequential mediation effect through therapist behavior and parental adherence in the models for these outcomes. The study proposes potential mediating mechanisms unique to the nondirective intervention and complements previous findings on mediator processes in favor of the behavioral group. Trial registration ClinicalTrials.gov NCT01350986.
| S-EPMC9444695 | biostudies-literature
Project description:Hydroquinone meroterpenoids, especially those derived from marine sponges, display a wide range of biological activities. However, use of these compounds is limited by their inaccessibility; there is no sustainable supply of these compounds. Furthermore, our knowledge of their metabolic origin remains completely unstudied. In this review, an in depth structural analysis of sponge merotriterpenoids, including the adociasulfate family of kinesin motor protein inhibitors, provides insight into their biosynthesis. Several key structural features provide clues to the relationships between compounds. All adociasulfates appear to be derived from only four different hydroquinone hexaprenyl diphosphate precursors, each varying in the number and position of epoxidations. Proton-initiated cyclization of these precursors can lead to all carbon skeletons observed amongst sponge merotriterpenoids. Consideration of the enzymes involved in the proposed biosynthetic route suggests a bacterial source, and a hypothetical gene cluster was constructed that may facilitate discovery of the authentic pathway from the sponge metagenome. A similar rationale can be extended to other sponge meroterpenoids, for which no biosynthetic pathways have yet been identified.
| S-EPMC5618424 | biostudies-literature
Project description:The study objective was to explore the experiences of parents of children (6-17 years) with complex mental healthcare needs in accessing healthcare services in Alberta, Canada. Parents were interviewed using a semi-structured guide with open-ended and probing questions. Interviews were audio recorded and transcribed verbatim. Thematic analysis revealed three main themes: (1) Fragmented healthcare services profoundly impacted participants' experience of mental health care due to (a) a lack of a collaborative approach across disciplines in the healthcare system; (b) unavailability of information related to mental health care and (c) a lack of patient-centred care. (2) Navigating the complex healthcare system was difficult due to fragmented services and was hindered by gaps in accessing and receiving care, lack of continuity of care and lack of resources. (3) Distressed parents discussed the emotional challenges, financial burdens, self-advocacy and stigma they experienced in navigating the system. Parents offered insights into potential solutions to these gaps. Parents recommended the creation of a one-stop shop service with a team approach led by a navigator to facilitate and support navigations across healthcare services that work collaboratively across disciplines among healthcare services and across sectors inclusive of social services, education, policing and community programmes.
| S-EPMC9667073 | biostudies-literature
Project description:BackgroundDespite the growing number of mobile health (mHealth) interventions targeting childhood obesity, few studies have characterized user typologies derived from individuals' patterns of interactions with specific app features (digital phenotypes).ObjectiveThis study aims to identify digital phenotypes among 214 parent-child dyads who used the Aim2Be mHealth app as part of a randomized controlled trial conducted between 2019 and 2020, and explores whether participants' characteristics and health outcomes differed across phenotypes.MethodsLatent class analysis was used to identify distinct parent and child phenotypes based on their use of the app's behavioral, gamified, and social features over 3 months. Multinomial logistic regression models were used to assess whether the phenotypes differed by demographic characteristics. Covariate-adjusted mixed-effect models evaluated changes in BMI z scores (zBMI), diet, physical activity, and screen time across phenotypes.ResultsAmong parents, 5 digital phenotypes were identified: socially engaged (35/214, 16.3%), independently engaged (18/214, 8.4%) (socially and independently engaged parents are those who used mainly the social or the behavioral features of the app, respectively), fully engaged (26/214, 12.1%), partially engaged (32/214, 15%), and unengaged (103/214, 48.1%) users. Married parents were more likely to be fullyengaged than independently engaged (P=.02) or unengaged (P=.01) users. Socially engaged parents were older than fullyengaged (P=.02) and unengaged (P=.01) parents. The latent class analysis revealed 4 phenotypes among children: fully engaged (32/214, 15%), partially engaged (61/214, 28.5%), dabblers (42/214, 19.6%), and unengaged (79/214, 36.9%) users. Fully engaged children were younger than dabblers (P=.04) and unengaged (P=.003) children. Dabblers lived in higher-income households than fully and partiallyengaged children (P=.03 and P=.047, respectively). Fully engaged children were more likely to have fully engaged (P<.001) and partiallyengaged (P<.001) parents than unengaged children. Compared with unengaged children, fully and partiallyengaged children had decreased total sugar (P=.006 and P=.004, respectively) and energy intake (P=.03 and P=.04, respectively) after 3 months of app use. Partially engaged children also had decreased sugary beverage intake compared with unengaged children (P=.03). Similarly, children with fully engaged parents had decreased zBMI, whereas children with unengaged parents had increased zBMI over time (P=.005). Finally, children with independently engaged parents had decreased caloric intake, whereas children with unengaged parents had increased caloric intake over time (P=.02).ConclusionsFull parent-child engagement is critical for the success of mHealth interventions. Further research is needed to understand program design elements that can affect participants' engagement in supporting behavior change.Trial registrationClinicalTrials.gov NCT03651284; https://clinicaltrials.gov/ct2/show/NCT03651284.International registered report identifier (irrid)RR2-10.1186/s13063-020-4080-2.
| S-EPMC9221987 | biostudies-literature
Project description:High hyperdiploidy (HD) is the most common cytogenetic subtype of childhood acute lymphoblastic leukemia (ALL), and a higher incidence of HD has been reported in ALL patients with congenital cancer syndromes. We assessed the frequency of predisposing germline mutations in 57 HD-ALL patients from the California Childhood Leukemia Study via targeted sequencing of cancer-relevant genes. Three out of 57 patients (5.3%) harbored confirmed germline mutations that were likely causal, in NBN, ETV6, and FLT3, with an additional six patients (10.5%) harboring putative predisposing mutations that were rare in unselected individuals (<0.01% allele frequency in the Exome Aggregation Consortium, ExAC) and predicted functional (scaled CADD score ≥ 20) in known or potential ALL predisposition genes (SH2B3, CREBBP, PMS2, MLL, ABL1, and MYH9). Three additional patients carried rare and predicted damaging germline mutations in GAB2, a known activator of the ERK/MAPK and PI3K/AKT pathways and binding partner of PTPN11-encoded SHP2. The frequency of rare and predicted functional germline GAB2 mutations was significantly higher in our patients (2.6%) than in ExAC (0.28%, P = 4.4 × 10-3 ), an observation that was replicated in ALL patients from the TARGET project (P = .034). We cloned patient GAB2 mutations and expressed mutant proteins in HEK293 cells and found that frameshift mutation P621fs led to reduced SHP2 binding and ERK1/2 phosphorylation but significantly increased AKT phosphorylation, suggesting possible RAS-independent leukemogenic effects. Our results support a significant contribution of rare, high penetrance germline mutations to HD-ALL etiology, and pinpoint GAB2 as a putative novel ALL predisposition gene.
| S-EPMC6684857 | biostudies-literature
Project description:OBJECTIVE:Maternal hemodynamics in pregnancy is associated with fetal growth and birth weight, which in turn are associated with offspring cardiovascular disease later in life. The aim of this study was to quantify the extent to which birth weight is associated with cardiac structure and function in adolescence. METHODS:A subset of offspring (n = 1964; 55% female) of the Avon Longitudinal Study of Parents and Children were examined with echocardiography at a mean age of 17.7 (SD, 0.3) years. The associations of birth-weight Z-score for sex and gestational age with cardiac structure (assessed by relative wall thickness, left ventricular mass index (LVMI) and left atrial diameter index), systolic function (assessed by ejection fraction and left ventricular wall velocity) and diastolic function (assessed by early/late mitral inflow velocity (E/A) and early mitral inflow velocity/mitral annular early diastolic velocity (E/e')) were evaluated. Linear regression models were adjusted for several potential confounders, including maternal prepregnancy body mass index, age, level of education and smoking during pregnancy. RESULTS:Higher birth-weight Z-score was associated with lower E/A (mean difference, -0.024; 95% CI, -0.043 to -0.005) and E/e' (mean difference, -0.05; 95% CI, -0.10 to -0.001) and higher LVMI (mean difference, 0.38 g/m2.7 ; 95% CI, 0.09 to 0.67). There was no or inconsistent evidence of associations of birth-weight Z-score with relative wall thickness, left atrial diameter and measurements of systolic function. Further analyses suggested that the association between birth-weight Z-score and LVMI was driven mainly by an association observed in participants born small-for-gestational age and it did not persist when risk factors in adolescence were accounted for. CONCLUSIONS:Higher birth weight adjusted for sex and gestational age was associated with differences in measures of diastolic function in adolescence, but the observed associations were small. It remains to be determined the extent to which these associations translate into increased susceptibility to cardiovascular disease later in life. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
| S-EPMC6771817 | biostudies-other